AO-252 for Cancer

Recruiting at 4 trial locations

Overseen By Robbin Frnka, VP/Clinops

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: A2A Pharmaceuticals Inc.

Must not be taking: CYP3A4 inhibitors, inducers

Disqualifiers: Brain metastases, Other malignancy, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

144 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, AO-252, for safety and effectiveness in patients with advanced or hard-to-treat cancers like TNBC, HGSOC, and endometrial cancer. Researchers will study how the drug works in the body and its potential to reduce tumors.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot take strong or moderate CYP3A4 inhibitors or inducers within 14 days before starting the study drug.

What safety data exists for AO-252 in humans?

The safety of oral cancer treatments like AO-252 can be challenging due to potential side effects, which may require dose adjustments or treatment interruptions. Common issues include skin, stomach, lung, and heart problems, and careful monitoring is recommended to manage these risks. ^{1 2 3 4 5}

How is the drug AO-252 different from other cancer treatments?

The drug AO-252 is unique because it may involve targeting the epidermal growth factor receptor (EGFR), which is overexpressed in many cancers, and could potentially act as a radiation sensitizer, enhancing the effectiveness of radiation therapy by making cancer cells more sensitive to it. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for adults with certain advanced solid tumors like TNBC, ovarian, peritoneal, fallopian-tube or serous endometrial cancer. Participants must have specific genetic mutations (TP53), be past a first line of chemotherapy and not suitable for standard treatments. They need to be relatively healthy otherwise, not pregnant or breastfeeding, willing to use contraception and without recent other cancers or serious illnesses.

Inclusion Criteria

I have TNBC, HGSOC, primary peritoneal, fallopian-tube, or serous endometrial cancer.

I am 18 years old or older.

You are expected to live for at least 3 more months.

Exclusion Criteria

You have a heart condition that shows up on an ECG test.

I have brain metastases or leptomeningeal disease that hasn't been treated or is causing symptoms.

I have fluid buildup that hasn't improved with treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants will be assigned to dose levels to determine the maximum tolerated dose and recommended Phase 2 dose

12 months

Dose Expansion

Participants will be assigned to a dose level determined in the Dose Escalation phase to further assess safety and efficacy

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AO-252

Trial Overview The study tests AO-252, an oral drug for advanced solid tumors. It aims to find the safest and most effective dose. The focus is on how well patients tolerate it and its impact on their cancer.

Participant Groups

Group I: Part 2: Dose Expansion Experimental Treatment 1 Intervention

After doses are decided in Part 1, participants entering part 2 will be assigned to a dose level.

Group II: Part 1: Dose Escalation Experimental Treatment 1 Intervention

Participants will be assigned to dose levels.

Who Is Running the Clinical Trial?

A2A Pharmaceuticals Inc.

Lead Sponsor

Trials

1

Recruited

140+

Findings from Research

In a study of 443 cancer outpatients starting oral antineoplastic agents (OAAs), over half (53.0%) required treatment adjustments within the first 100 days due to adverse events (AEs), highlighting the need for careful monitoring.

Specific factors such as treatment with sorafenib, lower performance status, and being on first-line therapy were linked to a higher likelihood of needing dose reductions or interruptions, indicating that certain patients may require closer observation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral antineoplastic agents: assessment of safety and dose adjustments in clinical practice. Escudero-Vilaplana, V., Revuelta-Herrero, JL., Collado-Borrell, R., et al.[2019]

A study analyzing 202 adverse events (AEs) reported by patients on health forums found that musculoskeletal disorders were reported more frequently than in the French pharmacovigilance database (FPVD), suggesting patients may experience and discuss these issues more openly online.

In contrast, skin disorders were reported less frequently on patient websites compared to the FPVD, and overall, the AEs shared by patients were less serious than those recorded in the FPVD, indicating a potential difference in the severity of AEs perceived by patients versus those documented in formal reporting systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Undesirable effects related to oral antineoplastic drugs: comparison between patients' internet narratives and a national pharmacovigilance database. Pages, A., Bondon-Guitton, E., Montastruc, JL., et al.[2021]

A machine-learning model was developed using data from 4638 patients across 16 FDA-approved small molecule kinase inhibitors (SMKIs) to analyze the relationship between kinase targets and adverse events (AEs), providing a new tool for predicting safety risks in cancer treatments.

The model not only helps identify potential kinase-inhibitor adverse event pairs but also serves as a precision medicine tool to enhance patient safety by forecasting clinical safety signals and aiding in the development of safer SMKI therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decoding kinase-adverse event associations for small molecule kinase inhibitors. Gong, X., Hu, M., Liu, J., et al.[2022]

Targeted therapies for non-small cell lung cancer (NSCLC) have significantly improved treatment options, but their effectiveness can be compromised by issues like poor patient adherence and adverse events.

The review highlights the need for standardized monitoring protocols for the various toxicities associated with these therapies, which can include skin, gastrointestinal, lung, and heart-related side effects, to ensure better patient management and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer. Hines, JB., Bowar, B., Levine, E., et al.[2023]

The review highlights significant safety challenges associated with oral agents for cancer (OACs), including medication errors and increased toxicity risks for both patients and healthcare providers.

As the number of OACs grows, there is a pressing need for updated safety standards and practices to mitigate risks and protect patients, caregivers, and healthcare professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral agents for cancer: safety challenges and recommendations. Rudnitzki, T., McMahon, D.[2017]

The novel nanoparticle therapy, C-siPLK1-NP, effectively targets EGFR in non-small cell lung cancer (NSCLC) cells, reduces PLK1 expression, and induces cell death, demonstrating its potential as a targeted treatment.

C-siPLK1-NP shows a synergistic effect when combined with radiation therapy, leading to reduced tumor growth and prolonged survival in an orthotopic lung tumor model, suggesting its efficacy as a radiation sensitizer for NSCLC and potentially other EGFR-positive cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PLK1 and EGFR targeted nanoparticle as a radiation sensitizer for non-small cell lung cancer. Reda, M., Ngamcherdtrakul, W., Gu, S., et al.[2023]

C225 significantly enhances the effectiveness of radiotherapy in treating tumors, with a notable reduction in the radiation dose required for tumor control when administered both during and after treatment.

Continuing C225 treatment after radiotherapy not only improves tumor curability but also delays tumor recurrence, suggesting that maintenance therapy could be a key strategy in future cancer treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Importance of maintenance therapy in C225-induced enhancement of tumor control by fractionated radiation. Milas, L., Fang, FM., Mason, KA., et al.[2018]

In a study of 65 patients with recurrent or metastatic oral squamous cell carcinoma, the combination of cetuximab and platinum-based chemotherapy showed a disease control rate of 67.7% and a median overall survival of 12.1 months, indicating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with the most common severe side effects being skin rash (9.2%) and leukopenia (6.2%), and importantly, none of the adverse events were fatal, highlighting the safety of this therapeutic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter retrospective study of cetuximab plus platinum-based chemotherapy for recurrent or metastatic oral squamous cell carcinoma. Yanamoto, S., Umeda, M., Kioi, M., et al.[2019]

In a phase II study involving 20 patients with recurrent oral cavity cancer after salvage surgery, adjuvant treatment with toripalimab showed a 1-year progression-free survival (PFS) rate of 58.2%, which is significantly better than a real-world reference cohort.

The treatment was well-tolerated, with no severe toxicities reported, and the efficacy appeared to be enhanced in patients with higher combined positive scores (CPS) and a higher proportion of peripheral blood B cells, suggesting potential biomarkers for treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant PD-1 antibody in recurrent, previously irradiated oral cavity cancer treated with salvage surgery. Dou, S., Zhang, L., Li, R., et al.[2023]

The EGFR inhibitor PD153035 effectively inhibited the growth of oral squamous cell carcinoma (OSCC) cells in vitro, delayed their cell cycle progression, and induced apoptosis, suggesting its potential as a therapeutic agent.

In vivo studies demonstrated that PD153035 not only reduced tumor growth in a mouse model but also prevented OSCC development in a hamster model, indicating its efficacy in both treatment and prevention of this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic and preventive effects of an epidermal growth factor receptor inhibitor on oral squamous cell carcinoma. Ge, H., Liu, H., Fu, Z., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Oral antineoplastic agents: assessment of safety and dose adjustments in clinical practice. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Undesirable effects related to oral antineoplastic drugs: comparison between patients' internet narratives and a national pharmacovigilance database. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Decoding kinase-adverse event associations for small molecule kinase inhibitors. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Oral agents for cancer: safety challenges and recommendations. [2017]

6. Ireland pubmed.ncbi.nlm.nih.gov

PLK1 and EGFR targeted nanoparticle as a radiation sensitizer for non-small cell lung cancer. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Importance of maintenance therapy in C225-induced enhancement of tumor control by fractionated radiation. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

Multicenter retrospective study of cetuximab plus platinum-based chemotherapy for recurrent or metastatic oral squamous cell carcinoma. [2019]

9. Ireland pubmed.ncbi.nlm.nih.gov

Adjuvant PD-1 antibody in recurrent, previously irradiated oral cavity cancer treated with salvage surgery. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Therapeutic and preventive effects of an epidermal growth factor receptor inhibitor on oral squamous cell carcinoma. [2018]